Stroke is one of the leading causes of death in humans. 80% or more of all stroke patients suffer ischemic cerebral infarction[1]. Despite the considerable amount of research conducted on the subject, treatment of stroke continues to be limited to thrombolytic therapy performed within 4.5 hours after onset using tissue plasminogen activator (tPA). Supportive care and rehabilitation have only been established for patients in the chronic stage of ischemic cerebral infarction. Thus, an approach involving alternative treatment is required in order to improve the functional outcome of patients.
According to recent research, various stem cells and progenitor cells have been demonstrated to be mobilized from the bone marrow to the peripheral blood in various disorders including ischemic cerebral infarction. These stem cells include endothelial progenitor cells (EPC), hematopoietic stem cells and CD31-positive cells (vascular progenitor cells), and contribute to vascularization in the brain. In addition to these cell types, mesenchymal stem cells (MSC) release neurotrophic factors and enhance functional recovery following ischemic cerebral infarction [2]. More importantly, these MSCs include small numbers of pluripotent cells capable of differentiating into neuronal cells [3]. Recently, Dezawa, et al. discovered a unique type of stem cell in dermal fibroblasts and adult human mesenchymal stem cells such as MSC. These cells account for several percent of all MSC, and since they are resistant to stress, have been named multilineage-differentiating stress enduring (MUSE) cells [4]. These cells can be efficiently isolated as cells positive for stage specific embryonic antigen (SSEA)-3, commonly known cell surface marker for pluripotent stem cells such as human embryonic stem (ES) cells. Muse cells can be efficiently separated from the human bone marrow and dermal fibroblasts by using SSEA-3 antibody in FACS [4]. Muse cells are self-renewable, express genes associated with pluripotency such as Nanog, Oct3/4 or Sox2, and are able to differentiate into endodermal, exodermal and mesodermal cells from a single cell. When induced by cytokines, Muse cells differentiate into neuron marker-positive cells at the extremely high rate of about 90% [5]. According to the results of animal experiments, Muse cells act as tissue repair cells when administrated in vivo. Animal models showed that Muse cells migrate towards damaged tissue, and in several animal disease models, spontaneously differentiate into cells compatible to the tissue they homed after integration into the damaged tissue [4]. In actuality, when injected into the infarcted brains of mice, Muse cells were incorporated in tissue after having settled in the brain of the host, expressed neuron markers, and remarkably enhanced functional recovery [6]. Differing from well known pluripotent stem cells, namely ES cells and induced pluripotent stem (iPS) cells, Muse cells have low telomerase activity and do not form tumors when transplanted into immunodeficient mouse testes [5,7].